Early response evaluation by single cell signaling profiling in acute myeloid leukemia

Nat Commun. 2023 Jan 7;14(1):115. doi: 10.1038/s41467-022-35624-4.

Abstract

Aberrant pro-survival signaling is a hallmark of cancer cells, but the response to chemotherapy is poorly understood. In this study, we investigate the initial signaling response to standard induction chemotherapy in a cohort of 32 acute myeloid leukemia (AML) patients, using 36-dimensional mass cytometry. Through supervised and unsupervised machine learning approaches, we find that reduction of extracellular-signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation in the myeloid cell compartment 24 h post-chemotherapy is a significant predictor of patient 5-year overall survival in this cohort. Validation by RNA sequencing shows induction of MAPK target gene expression in patients with high phospho-ERK1/2 24 h post-chemotherapy, while proteomics confirm an increase of the p38 prime target MAPK activated protein kinase 2 (MAPKAPK2). In this study, we demonstrate that mass cytometry can be a valuable tool for early response evaluation in AML and elucidate the potential of functional signaling analyses in precision oncology diagnostics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / metabolism
  • MAP Kinase Signaling System / physiology
  • Phosphorylation
  • Precision Medicine*
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • p38 Mitogen-Activated Protein Kinases